Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-11-10
2000-09-05
Eyler, Yvonne
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 721, 435 723, 436 63, 436 64, G01N 3353, G01N 33555, G01N 33567, G01N 33574
Patent
active
061141283
DESCRIPTION:
BRIEF SUMMARY
The present invention relates generally to a method of predicting the therapeutic response of a drug. More specifically, the invention relates to a method of predicting the therapeutic response of a drug directed towards a malignant tumour in a human patient, and to a diagnostic kit in order to enable the method to be applied routinely.
The importance of lymphocytes in the control by the immune system of malignant tumours as well as the necessary presence of these cells in tumours has been known for several decades. However, nobody has studied the presence of lymphocytes in tumours, using fine needle aspirates, in relation to immunotherapy and the effect of treating a disease with a successful outcome.
The outcome of a treatment of a patient with a specific drug against a malignant tumour is often unpredictable. Only about 15-20% of the patients respond to the medication of each type of treatment. The patients receiving the medication are subjected to an unnecessary suffering since adverse reactions often are obtained from the drug used. Mostly, the effect of the drug is not shown before 3-6 months of treatment. A drug for treatment of a malignant tumour is often expensive and a considerable cost reduction would be obtained if the drug used is effective. It would therefore be of great importance if patients with a high probability to respond could be identified before the onset of treatment.
For example, interferon-alpha (IFN-.alpha.) has a documented activity,against malignant melanoma. Five to ten million units IFN-.alpha. three times weekly seems, at the cost of reasonable side effects, (Legha et al.) to be an optimal dose range. The treatment efficacy varies in different studies (Creagan et al., Gundersen, Legha et al.) and the over-all response rate (CR+PR) to IFN-.alpha. alone is only about 20% (Creagan et al., Legha et al.). It would therefore be a considerable improvement if patients with a high probability to respond to this treatment could be identified using predictive tests.
Besides having an antiproliferative activity (Balkwill et al,.Riviere et al.), the antitumour effect of IFN-.alpha. can be due to modulation of tumour cells, e.g. induction of 2,5-A synthetase or increased expression of cell surface proteins, MHC I and tumour associated antigens which are of importance for the immunological control of tumours. In addition, IFN-.alpha. modulates several immune functions (12 Friedman). There are still no firm data demonstrating which of these activities of IFN-.alpha. that is the most important one for the antitumour activity or if they all contribute.
As IFN-.alpha. modulates the activity of various cells in the immune system, e.g. activation of machrophages, NK-cells, cytotoxic T-cells and B-cell function (Friedman et al.), the therapeutic effect might depend on the immune status of the patients when IFN-.alpha. therapy is initiated.
Immune reactivity to malignant melanoma has been demonstrated as spontaneous regression (Mc Govern et al., Sondergaard et al., Ronan et al., Kang et al.), occurence of antibodies of prognostic significans against melanoma associated antigens and specific cytotoxic lymphocytes (Abershold et al.). Conflicting results have, however, been reported on the prognostic significance of lymphocytic infiltration in primary malignant melanoma. Some studies found a significantly better prognosis if the primary lesions had a prominent infiltration of lymphocytes (Hansen et al., Larsen et al.) whereas others found no such correlation (Balch et al.) Three studies also found a relation between tumour thickness and lymphocytic infiltration (Balch et al., Hansen et al., Larsen et al.). This discrepancy was further studied by Mc Govern et al. who found the lymphocytic infiltration at the base of the melanoma to be of prognostic significance in contrast to lymphocytic infiltration at the margins. These authors also found that the lymphocytic infiltration at the tumour base was reduced as tumour thickness increased. A reasonable strategy to treat malignant melanoma would therefore,
REFERENCES:
Itoh, et al., Cancer Immunol. Immunother., vol. 33, pp. 238-246, 1991.
Aebersold, P. et al., "Lysis of Autologous Melanoma Cells by Tumor-Infiltrating Lymphocytes: Association With Clinical Response", Journal of the National Cancer Institute, 83(13): 932-937 (Jul. 3, 1991).
Balch et al., "A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods", Ann. Surg., 188(6): 732-742 (Dec. 1978).
Balkwill, F., "Peptide Regulatory Factors", The Lancet: 1060-1063 (May 13, 1989).
Balkwill, F.R. et al., "Human Interfon Inhibits the Growth of Established Human Breast Tumors in the Nude Mouse", Int. J. Cancer, 30: 231-235 (1982).
Breard, J. et al., "A Monoclonal Antibody Reactive with Human Peripheral Blood Monocytes", The Journal of Immunology, 124(4): 1943-1948 (Apr. 1980).
Cosimi, A. et al., "Use of Monoclonal Antibodies to T-Cell Subsets for Immunologic Monitoring and Treatment in Recipients of Renal Allografts", The New England Journal of Medicine, 305(6): 308-314 (Aug. 6, 1981).
Creagan, E.T. et al., "Recombinant Interferons in the Management of Advanced Malignant Melanoma", Am J. Clin Oncol (CCT) 11(6): 652-659 (1988).
Eisenthal, A. et al., "Phenotypic and Functional Profile of Peripheral Blood Mononuclear Cells Isolated from Melanoma Patients Undergoing Combined Immunotherapy and Chemotherapy", Cancer Immunol Immunther, 37(6): 367-372 (Dec. 6, 1993).
Friedman, R. et al., "Interfeons with Special Emphasis on the Immune System", Advances in Immunology, 34: 97-140 (1983).
Gresser, I., "Biologic Effects of Interferons", The Journal of Investigative Dermatology, 95(6): 66S-71S (1990).
Gundersen, S. et al., "Interferon in Combination with Vinblastine in Advanced Malignant Melanoma", Cancer, 64: 1617-1619 (Oct. 15, 1989).
Hakansson, A. et al., "Tumor-Infiltrating Lymphocytes in Metastatic Malignant Melanoma and Response to Interferon Alpha Treatment", British Journal of Cancer, 74: 670-676 (1996).
Hansen, M. et al., "Tumor Thickness and Lymphocytic Infiltration in Malignant Melanoma of the Head and Neck", The American Journal of Surgery, 128: 557-561 (Oct. 1974).
Hersey, P. et al., "Immunohistological Relation Between DR Antigen Expression on Melanoma Cells and Infiltration by CD8+ T Cells", Pathology, 22: 133-139 (1990).
Hurwitz, P., "Spontaneous Regression of Metastatic Melanoma", Annals of Plastic Surgery, 26(4): 403-406 (Apr. 1991).
Hutchinson, G.H. et al., "Differential Immune Reactivity of Tumour-Intrinsic and Peripheral-Blood Lymphocytes Against Autoplastic Colurectal Carcinoma Cells," Br. J. Cancer, 44:396-402 (1981).
Jones, P. et al., "Prolonged Survival for Melanoma Patients with Elevated IgM Antibody to Oncofetal Antigen", JNCI. 66,(2): 249-254 (1981).
Kang, S. et al., "Histologic Regression in Malignant Melanoma: An Interobserver Concordance Study", Journal of Cutaneous Pathology: 126-129 (1993).
Kirkwood, J. et al., "Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Meloma: The Eastern Cooperative Oncology Group Trial EST 1684", Journal of Clinical Oncology, 14(1): 7-17 (Jan. 1996).
Klein, E. et al., "Separation and Characteristics of Tumor-Infiltrating Lymphocytes in Man", Contemporary Topics in Immunology, (10): 79-107 (1980).
Knop, J., "Immunologic Effects of Interferon", The Journal of Investigative Dermatology, 95(6): 72S-74S (Dec. 1990).
Kornstein, M. et al., "Immunoperoxidase Localization of Lymphocyte Subsets in the Host Response to Melanoma and Nevi", Cancer Research, 43: 2749-2753 (Jun. 1983).
Larsen, T. et al., "A Retrospective Histological Study of 669 Cases Primary Cutaneous Malignant melanoma in Clinical Stage I", Acta path. nicrobiol. scand. Sect. A. 86: 523-530 (1978).
Legha, S., "Current Therapy for Malignant Melanoma", Seminars in Oncology, 16(1) Suppl 1: 34-44 (Feb. 1989).
McGovern, V. et al., "Lymphocyctic Infiltration and Survival in Malignant Melanoma", Pathology of Malignant Melanoma: 341-344 (1981).
McGovern, V.J. "Spontaneous Regression
Gustafsson Bertil
H.ang.kansson Annika
H.ang.kansson Leif
Eyler Yvonne
Landstinget I Ostergotland
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